Back to resultsCART-PSMA Cells for Advanced Prostate Cancer
Primary Purpose
Prostate Cancer
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
CART-PSMA cells
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer
Eligibility Criteria
Inclusion Criteria: All participants must have the ability to understand and the willingness to sign a written informed consent. Histologic confirmation of prostate cancer. Tumor expressing PSMA as demonstrated by immunohistochemistry analysis or other methods. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2. Under general air conditions, blood oxygen saturation >90%. Adequate liver function, specifically alanine aminotransferase (ALT) < 3 times of upper limit of normal (ULN), aspartate transferase (AST)< 3 times of ULN, serum bilirubin and alkaline phosphatase < 2 times of ULN. Adequate renal function, specifically serum creatinine < 2.0 mg/dl. Adequate cardiac function, specifically left ventricular ejection fraction (LVEF)≥50%. Hemoglobin concentration ≥80g/L. The side effects brought by the latest treatment should be recovered, and the latest chemotherapy should be at least 7 days before; At least three t½ have passed since the latest immunotherapy. Exclusion Criteria: Patients with other malignant tumors or major diseases. Patients who are already undergoing other clinical drug trials or other gene therapy or cell therapy. Patients with uncontrolled active infection. Patients with active hepatitis B or hepatitis C infection. Patients with human immunodeficiency virus (HIV) infection. Patients who are being treated with immunosuppressive agents or systemic steroids (other than inhalation therapy). Patients with various types of serious heart disease or a history of severe cerebrovascular disease. Patients with congenital immune deficiency diseases or bone marrow deficiency diseases. Patients with active autoimmune disease, including connective tissue disease, uveitis, inflammatory bowel disease, or multiple sclerosis; or a history of severe (as judged by the physician-investigator) autoimmune disease requiring prolonged immunosuppressive therapy. Patients with active medical condition that, in the opinion of the physician-investigator, would substantially increase the risk of uncontrollable CRS (cytokine release syndrome) or CAR Neurotoxicity.
Sites / Locations
- Chinese PLA General HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
autologous CART-PSMA cells
Arm Description
Outcomes
Primary Outcome Measures
Occurrence of study related adverse events, laboratory toxicities and clinical events that are possibly, likely, or definitely related to study participation.
Assessing the type, frequency, severity, and duration of adverse events as a result of CART-PSMA cell infusion via physical, laboratory and imaging examination.
Secondary Outcome Measures
The persistence, accumulation, and migration of CART-PSMA cells.
Assessing the trafficking of CART-PSMA cells in the peripheral blood by quantifying the mRNA of CAR gene at the time of each infusion as well as at each time of follow-up blood collection. Peripheral blood will be collected prior to the initial infusion and will be set as baseline.
Overall survival (OS)
Estimating median OS from CART-PSMA cell infusion to the event date (death) or last contact date (censor date) by Kaplan Meier methods.
Progression-free survival (PFS)
Estimating median PFS by survival without biochemical (PSA) or radiographic evidence of disease progression or relapse from CART-PSMA cell infusion to event date (progression/relapse or death); the censor date: off protocol therapy date (required disallowed treatment or withdrawal of consent for further therapy) or last contact date.
Patterns of change in PSA (prostate-specific antigen)
Assessing PSA response by the percentage of change in PSA from baseline to the defined time-frame on therapy (or earlier if patients discontinue therapy prior to the time-frame) as well as the maximum decline in PSA that occurs at any point during CART-PSMA cell infusion.
Serum cytokine profile
Assessing potential cytokine release syndrome (CRS) toxicity and CART cell effector function, sequential serum samples by analysis of Th1/Th2 cytokines (e.g., IL-2, IFNgamma, TNFalpha, IL-10, GMCSF, IL-6, MIP-1alpha) before and after CART-PSMA cell infusion.
Phenotypes and frequencies of immune cell subsets in the peripheral blood pre- and post-therapy
Assessing phenotypes and frequencies of immune cell subsets in the peripheral blood, T cell subsets and phenotypes utilising groups of labelled antibodies.
Changes in circulating tumor cells in peripheral blood
Assessing changes in levels of circulating tumor cells (CTC) to investigate if decreases in CTC levels correlate with response.
Circulating cell-free deoxyribonucleic acid (cfDNA) in peripheral blood
Assessing changes in levels of cfDNA to investigate if decreases in cfDNA levels correlate with response.
Full Information
NCT ID
NCT05656573
First Posted
December 1, 2022
Last Updated
December 12, 2022
Sponsor
Nova Therapeutics LLC
Collaborators
Chinese PLA General Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05656573
Brief Title
CART-PSMA Cells for Advanced Prostate Cancer
Official Title
Phase I Study of CART-PSMA Cells in Patients With Advanced Prostate Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2023 (Anticipated)
Primary Completion Date
December 1, 2024 (Anticipated)
Study Completion Date
December 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nova Therapeutics LLC
Collaborators
Chinese PLA General Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a single center, open-label phase 1 study to assess the safety and feasibility of PSMA-specific CAR modified autologous T cells (CART-PSMA cells) in patients with advanced prostate cancer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
autologous CART-PSMA cells
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
CART-PSMA cells
Intervention Description
This study consists of 2 parts:
Part A (Dose Escalation): The investigators are looking the highest dose of the study intervention that can be administered safely without severe or unmanageable side effects in participants that advanced prostate cancer.
Up to 4 dosing cohorts, with up to 3 subjects enrolled in each cohort, will be explored as follows:
cohort 1： CART-PSMA cells 1-3x10^7 on Day 0;
cohort 2： CART-PSMA cells 1-3x10^8 on Day 0;
cohort 3： CART-PSMA cells 1-3x10^7 on Day 0,following lymphodepleting chemotherapy with cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day given over 3 days;
cohort 4： CART-PSMA cells 1-3x10^8 on Day 0,following lymphodepleting chemotherapy with cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day given over 3 days;
Part B (Expansion Cohort): Participants will be treated at the respective dose (at or below the Maximum Tolerated Dose), as determined during Part A (Dose Escalation).
Primary Outcome Measure Information:
Title
Occurrence of study related adverse events, laboratory toxicities and clinical events that are possibly, likely, or definitely related to study participation.
Description
Assessing the type, frequency, severity, and duration of adverse events as a result of CART-PSMA cell infusion via physical, laboratory and imaging examination.
Time Frame
Up to 15 years
Secondary Outcome Measure Information:
Title
The persistence, accumulation, and migration of CART-PSMA cells.
Description
Assessing the trafficking of CART-PSMA cells in the peripheral blood by quantifying the mRNA of CAR gene at the time of each infusion as well as at each time of follow-up blood collection. Peripheral blood will be collected prior to the initial infusion and will be set as baseline.
Time Frame
Up to 2 years
Title
Overall survival (OS)
Description
Estimating median OS from CART-PSMA cell infusion to the event date (death) or last contact date (censor date) by Kaplan Meier methods.
Time Frame
Up to 15 years
Title
Progression-free survival (PFS)
Description
Estimating median PFS by survival without biochemical (PSA) or radiographic evidence of disease progression or relapse from CART-PSMA cell infusion to event date (progression/relapse or death); the censor date: off protocol therapy date (required disallowed treatment or withdrawal of consent for further therapy) or last contact date.
Time Frame
Up to 15 years
Title
Patterns of change in PSA (prostate-specific antigen)
Description
Assessing PSA response by the percentage of change in PSA from baseline to the defined time-frame on therapy (or earlier if patients discontinue therapy prior to the time-frame) as well as the maximum decline in PSA that occurs at any point during CART-PSMA cell infusion.
Time Frame
Up to 5 years
Title
Serum cytokine profile
Description
Assessing potential cytokine release syndrome (CRS) toxicity and CART cell effector function, sequential serum samples by analysis of Th1/Th2 cytokines (e.g., IL-2, IFNgamma, TNFalpha, IL-10, GMCSF, IL-6, MIP-1alpha) before and after CART-PSMA cell infusion.
Time Frame
Up to 2 years
Title
Phenotypes and frequencies of immune cell subsets in the peripheral blood pre- and post-therapy
Description
Assessing phenotypes and frequencies of immune cell subsets in the peripheral blood, T cell subsets and phenotypes utilising groups of labelled antibodies.
Time Frame
Up to 2 years
Title
Changes in circulating tumor cells in peripheral blood
Description
Assessing changes in levels of circulating tumor cells (CTC) to investigate if decreases in CTC levels correlate with response.
Time Frame
Up to 2 years
Title
Circulating cell-free deoxyribonucleic acid (cfDNA) in peripheral blood
Description
Assessing changes in levels of cfDNA to investigate if decreases in cfDNA levels correlate with response.
Time Frame
Up to 2 years
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
All participants must have the ability to understand and the willingness to sign a written informed consent.
Histologic confirmation of prostate cancer.
Tumor expressing PSMA as demonstrated by immunohistochemistry analysis or other methods.
Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
Under general air conditions, blood oxygen saturation >90%.
Adequate liver function, specifically alanine aminotransferase (ALT) < 3 times of upper limit of normal (ULN), aspartate transferase (AST)< 3 times of ULN, serum bilirubin and alkaline phosphatase < 2 times of ULN.
Adequate renal function, specifically serum creatinine < 2.0 mg/dl.
Adequate cardiac function, specifically left ventricular ejection fraction (LVEF)≥50%.
Hemoglobin concentration ≥80g/L.
The side effects brought by the latest treatment should be recovered, and the latest chemotherapy should be at least 7 days before; At least three t½ have passed since the latest immunotherapy.
Exclusion Criteria:
Patients with other malignant tumors or major diseases.
Patients who are already undergoing other clinical drug trials or other gene therapy or cell therapy.
Patients with uncontrolled active infection.
Patients with active hepatitis B or hepatitis C infection.
Patients with human immunodeficiency virus (HIV) infection.
Patients who are being treated with immunosuppressive agents or systemic steroids (other than inhalation therapy).
Patients with various types of serious heart disease or a history of severe cerebrovascular disease.
Patients with congenital immune deficiency diseases or bone marrow deficiency diseases.
Patients with active autoimmune disease, including connective tissue disease, uveitis, inflammatory bowel disease, or multiple sclerosis; or a history of severe (as judged by the physician-investigator) autoimmune disease requiring prolonged immunosuppressive therapy.
Patients with active medical condition that, in the opinion of the physician-investigator, would substantially increase the risk of uncontrollable CRS (cytokine release syndrome) or CAR Neurotoxicity.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jay Zhang, MD/PhD
Phone
858-205-4558
Email
jiezhang8@hotmail.com
Facility Information:
Facility Name
Chinese PLA General Hospital
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jay Zhang, MD/PhD
First Name & Middle Initial & Last Name & Degree
Xu Zhang, MD/PhD
First Name & Middle Initial & Last Name & Degree
Haixing Mai, MD/PhD
First Name & Middle Initial & Last Name & Degree
Yu Gao, MD/PhD
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
CART-PSMA Cells for Advanced Prostate Cancer
We'll reach out to this number within 24 hrs